System, device, and method for mixing liquids

ABSTRACT

A system, device, and method for mixing liquids involves pumping a first liquid into a first pump chamber of a pumping apparatus through a channel of the pumping apparatus and pumping a second liquid from a second pump chamber of the pumping apparatus into either the channel or the first pump chamber, preferably while the first liquid is being pumped into the first pump chamber, so that the two liquids are mixed within the pumping apparatus. The second liquid is preferably pumped in a pulsatile mode in which small quantities of the second liquid are pumped at intervals. The quantity and/or the interval can be dynamically adjusted to result in a predetermined concentration of the two liquids. The contents of the first pump chamber are pumped to a receptacle.

CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application may include subject matter related to one ormore of the following commonly-owned United States patent applications,each of which was filed on even date herewith and is hereby incorporatedherein by reference in its entirety: U.S. patent application Ser. No.10/696,969 entitled SYSTEM, DEVICE, AND METHOD FOR MIXING A SUBSTANCEWITH A LIQUID (referred to herein as “Application D70”); U.S. patentapplication Ser. No. 10/696,818, now U.S. Pat. No. 7,086,700 entitledTWO-STAGE MIXING SYSTEM, APPARATUS, AND METHOD (referred to herein as“Application D72”); U.S. patent application Ser. No. 10/697,176 entitledSYSTEM AND METHOD FOR PUMPING FLUID USING A PUMP CASSETE (referred toherein as “Application D73”); U.S. patent application Ser. No.10/696,984 entitled DOOR LOCKING MECHANISM (referred to herein as“Application D74”); U.S. patent application Ser. No. 10/697,450 entitledBEZEL ASSEMBLY FOR PNEUMATIC CONTROL (referred to herein as “ApplicationD75”); U.S. patent application Ser. No. 10/697,862 entitled PUMP CASSETEWITH SPIKING ASSEMBLY (referred to herein as “Application D84”); andU.S. patent application Ser. No. 10/696,990 entitled PUMP CASSETTE BANK(referred to herein as “Application D85”).

FIELD OF THE INVENTION

The present invention relates generally to pumping liquids, and moreparticularly to a system, device, and method for mixing liquids.

BACKGROUND OF THE INVENTION

Millions of people receive blood transfusions each year. Althoughhelpful in many cases, blood transfusions have associated risks. Amongothers, there is a risk that microorganisms capable of causing disease(i.e., pathogens) could pass from the donor blood to the ultimate bloodrecipient. For example, untreated blood used in a blood transfusioncould have pathogens causing the West Nile Virus, or AIDS. It thus iscritical for the public health to ensure that transfused blood issubstantially free of pathogens.

The medical community has responded to this need by developing varioustechniques for removing known and unknown pathogens from donated blood.One technique involves mixing precise amounts of a diluted anti-pathogencompound with blood. Some time after mixing, a rinsing process removesthe anti-pathogen compound from the blood. One complexity with thisprocess, however, is the fact that the diluted anti-pathogen compoundhas a very short shelf life (e.g., on the order of about four hours).Accordingly, the diluted anti-pathogen compound must be produced arelatively short time before it is mixed with blood.

The anti-pathogen compound is not easy to handle before it is diluted.To the contrary, it has a very high pH (e.g., on the order of 11.0 orhigher) and thus, is highly caustic and toxic. Mere contact with theundiluted solution can melt plastic, or burn flesh. Because of theseundesirable properties, the undiluted solution typically is manuallydiluted by highly trained laboratory technicians that necessarily mustbe protected from direct contact with it. Consequently, laboratorytechnicians often are required to wear relatively impermeable protectivegear while diluting the solution behind a chemical laminar flowhood.Such a process, however, is inherently slow, imprecise, and costly dueto the multitude of safety requirements. Moreover, even with safeguards,diluting the undiluted solution still poses a risk to the laboratorytechnician.

SUMMARY OF THE INVENTION

In accordance with one aspect of the invention, mixing liquids involvespumping a first liquid into a first pump chamber of a pumping apparatusthrough a channel of the pumping apparatus and pumping a second liquidfrom a second pump chamber of the pumping apparatus into either thechannel or the first pump chamber, preferably while the first liquid isbeing pumped into the first pump chamber, so that the two liquids aremixed within the pumping apparatus. The second liquid is preferablypumped in a pulsatile mode in which small quantities of the secondliquid are pumped at intervals. The quantity and/or the interval can bedynamically adjusted to result in a predetermined concentration of thetwo liquids. The contents of the first pump chamber are pumped to areceptacle.

In accordance with another aspect of the invention, a method for mixinga first liquid with a second liquid involves pumping a first liquid intoa first pump chamber of a pumping apparatus through a channel of thepumping apparatus and pumping a quantity of a second liquid from asecond pump chamber of the pumping apparatus into one of the channel andthe first pump chamber so as to mix the first liquid and the secondliquid within the pumping apparatus. The quantity of the second liquidis preferably pumped during the pumping of the first liquid. The pumpingapparatus may be a pneumatically operated pump cassette having variouspneumatically operated pump chambers and valves. The second liquid maybe pumped in a pulsatile mode. The pulse width and pulse interval may bedynamically adjusted to obtain a predetermined concentration of firstliquid and second liquid. The contents of the first pump chamber may bepumped to a receptacle.

In accordance with another aspect of the present invention, an apparatusfor mixing a first liquid with a second liquid includes a first pumpcontroller operatively coupled to pump a first liquid into a first pumpchamber of a pumping apparatus through a channel of the pumpingapparatus and a second pump controller operatively coupled to pump aquantity of a second liquid from a second pump chamber of the pumpingapparatus into one of the channel and the first pump chamber so as tomix the first liquid and the second liquid within the pumping apparatus.The quantity of the second liquid is preferably pumped during thepumping of the first liquid. The pumping apparatus may be apneumatically operated pump cassette having various pneumaticallyoperated pump chambers and valves. The second liquid may be pumped in apulsatile mode. The pulse width and pulse interval may be dynamicallyadjusted to obtain a predetermined concentration of first liquid andsecond liquid. The contents of the first pump chamber may be pumped to areceptacle. The apparatus may include a pump cassette interface forpneumatically operating the chambers and valves of the pump cassette.The pump cassette interface may include a limiter for limiting theamount of second liquid held by the second pump chamber.

In accordance with another aspect of the present invention, an apparatusfor mixing a first liquid with a second liquid includes means forpumping a first liquid into a first pump chamber of a pumping apparatusthrough a channel of the pumping apparatus and means for pumping aquantity of a second liquid from a second pump chamber of the pumpingapparatus into one of the channel and the first pump chamber so as tomix the first liquid and the second liquid within the pumping apparatus.

In accordance with another aspect of the present invention, a system formixing a first liquid with a second liquid includes a plurality of firstliquid containers, each containing a first liquid; a second liquidcontainer containing a second liquid; and a plurality of pumps, eachpump operatively coupled to mix first liquid from a respective one ofthe plurality of first liquid containers with second liquid from thesecond liquid container. The system may also include a processcontroller in communication with the plurality of pumps for coordinatingsaid mixing by the pumps.

In accordance with another aspect of the invention, red blood cellconcentrate is mixed with an anti-pathogen solution to form anincubation solution.

BRIEF DESCRIPTION OF THE DRAWINGS

In the accompanying drawings:

FIG. 1A shows an exemplary blood processing system having a plurality ofblood pumps in accordance with an embodiment of the present invention;

FIG. 1B shows an exemplary wiring diagram for one embodiment of theblood processing system shown in FIG. 1A;

FIG. 1C shows an exemplary wiring diagram for another embodiment of theblood processing system shown in FIG. 1A;

FIG. 2 shows an exemplary blood disposables set in accordance with anembodiment of the present invention;

FIG. 3A shows a front view of the pump cassette in accordance with anembodiment of the present invention;

FIG. 3B shows a rear view of the pump cassette in accordance with anembodiment of the present invention;

FIG. 4 shows a conceptual block diagram of the blood pump in accordancewith an embodiment of the present invention;

FIG. 5A is an architectural flow diagram showing the relationshipbetween the pneumatic control assembly and the other assemblies inaccordance with an embodiment of the present invention;

FIG. 5B shows an exemplary embodiment of the pneumatic control assemblyin accordance with an embodiment of the present invention;

FIG. 5C shows an exemplary embodiment of the air pump in accordance withan embodiment of the present invention;

FIG. 6A shows an exploded view of an exemplary front plate assembly inaccordance with an embodiment of the present invention;

FIG. 6B shows a front view of an exemplary bezel in accordance with anembodiment of the present invention;

FIG. 6C shows a rear view of an exemplary bezel in accordance with anembodiment of the present invention;

FIG. 6D shows a front view of an exemplary bezel gasket in accordancewith an embodiment of the present invention;

FIG. 6E shows a rear view of an exemplary bezel gasket in accordancewith an embodiment of the present invention;

FIG. 7A shows an exploded view of the door assembly in accordance withan embodiment of the present invention;

FIG. 7B shows a front perspective view of the door assembly inaccordance with an embodiment of the present invention;

FIG. 7C shows a rear perspective view of the door assembly in accordancewith an embodiment of the present invention, in which the cassettereceptacle is in a retracted position;

FIG. 7D shows a rear perspective view of the door assembly in accordancewith an embodiment of the present invention, in which the cassettereceptacle is in an open position;

FIG. 8 shows a side perspective view of the occluder assembly inaccordance with an embodiment of the present invention;

FIG. 9 shows a cross-sectional view of an occluder in accordance with anembodiment of the present invention;

FIG. 10 shows an exploded view of the occluder assembly in accordancewith an embodiment of the present invention;

FIG. 11 is a schematic diagram showing the pump cassette installed inthe blood pump in accordance with an embodiment of the presentinvention;

FIG. 12 shows a process flow diagram describing the compounding andblood treatment process, which is coordinated by the process controller,in accordance with an embodiment of the present invention;

FIGS. 13A-B show a process flow diagram showing additional details ofthe blood processing operations in accordance with an embodiment of thepresent invention;

FIG. 14 shows a process flow diagram describing the blood pump dry CITprocess in accordance with an embodiment of the present invention;

FIG. 15 shows a process flow diagram describing the blood pump workingsolution priming process in accordance with an embodiment of the presentinvention;

FIG. 16 shows a process flow diagram describing the blood pump wet CITprocess in accordance with an embodiment of the present invention;

FIGS. 17A-D show a process flow diagram describing the blood mixingprocess in accordance with an embodiment of the present invention;

FIG. 18 shows a process flow diagram describing the volumetriccalibration process in accordance with an embodiment of the presentinvention;

FIG. 19 shows a process flow diagram describing the process for manualblood pump teardown in accordance with an embodiment of the presentinvention; and

FIG. 20 shows a logic flow diagram showing exemplary logic 2000 formixing two liquids in accordance with an embodiment of the presentinvention.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT

Embodiments of the present invention provide for safely and efficientlymixing two liquids. In order to mix two liquids, a first liquid ispumped into a first pump chamber of a pumping apparatus through achannel of the pumping apparatus. A second liquid is pumped from asecond pump chamber of the pumping apparatus into either the channel orthe first pump chamber, preferably while the first liquid is beingpumped into the first pump chamber. In this way, the two liquids aremixed within the pumping apparatus, and, more specifically, within thechannel and/or the first pump chamber of the pumping apparatus. Thesecond liquid is preferably pumped in a pulsatile mode in which smallquantities of the second liquid are pumped at intervals, for example, asdescribed in U.S. Pat. No. 6,604,908, which is hereby incorporatedherein by reference in its entirety. The quantity and/or the intervalcan be dynamically adjusted to result in a predetermined concentrationof the two liquids. The contents of the first pump chamber are pumped toa receptacle.

FIG. 20 is a logic flow diagram showing exemplary logic 2000 for mixingtwo liquids in accordance with an embodiment of the present invention.Beginning in block 2002, the logic pumps a first liquid into a firstpump chamber of a pumping apparatus through a channel of the pumpingapparatus, in block 2004. The logic pumps a second liquid from a secondpump chamber of the pumping apparatus into one of the channel and thefirst pump chamber so as to mix the first liquid and the second liquidwithin the pumping apparatus, in block 2006. The logic dynamicallyadjusts the amount of second liquid pumped to obtain a predeterminedconcentration of first liquid and second liquid, in block 2008. Thelogic pumps the contents of the first pump chamber into a receptacle, inblock 2010. The various pumping and adjusting operations may be repeatedas necessary to process a predetermined quantity of liquids. The logic2000 ends in block 2099.

In exemplary embodiments of the present invention, the pumping apparatusis a disposable pump cassette. The pump cassette typically includes twopump chambers and various valves. The pump chambers and valves arepreferably operated pneumatically.

In exemplary embodiments of the present invention, an anti-pathogensolution is mixed with a red blood cell concentrate (RBCC) to form anincubation solution for reducing pathogens in the RBCC. Theanti-pathogen solution is prepared by mixing a caustic anti-pathogencompound known as PEN110 or INACTINE, which is an organic solvent with apH over 11 that is distributed by V.I. Technologies, Inc. of Watertown,Mass., with a buffer solution of sodium phosphate to a predeterminedconcentration (e.g., 1 part anti-pathogen compound to 99 parts buffersolution), preferably as described in Application D70. For convenience,this mixing of anti-pathogen compound with buffer solution may bereferred to hereinafter as “compounding,” and an apparatus that performssuch compounding may be referred to hereinafter as a “compounder” or“compounder pump.” The incubation solution is prepared by mixing theanti-pathogen solution with the RBCC to a predetermined concentration(e.g., 1 part anti-pathogen solution to 9 parts RBCC), as describedbelow. For convenience, this mixing of anti-pathogen solution with RBCCmay be referred to hereinafter as “blood processing,” and an apparatusthat performs such blood processing may be referred to hereinafter as a“blood pump.”

System Overview

FIG. 1A shows an exemplary blood processing system 100 having aplurality of blood pumps in accordance with an embodiment of the presentinvention. Among other things, the blood processing system 100 includesa single compounder pump 102 and ten essentially identical blood pumps104 organized as two banks of five blood pumps each. The compounder pump102 pumps buffer solution from a buffer solution container 110 into avial of anti-pathogen compound 108. The mixture, referred to as aworking solution, is pumped into a working solution container 112. Eachof the blood pumps 104 mixes working solution from the working solutioncontainer 112 with red blood cell concentrate (RBCC) from a RBCCcontainer 106 to form an incubation solution that is pumped into anincubation bag 118. The incubation solution is typically allowed toincubate for some period of time, after which it is rinsed to remove theanti-pathogen compound to produce a pathogen reduced blood product. Theblood processing system 100 typically also includes two sterile docks114 that are used by the operator to splice together plastic tubing asnecessary for various blood processing operations. The blood processingsystem 100 is controlled through a user interface 116.

FIG. 1B shows an exemplary wiring diagram for one embodiment of theblood processing system 100. The compounder pump 102 and the blood pumps104 are typically powered from a common 12-Volt external power supply126, and are controlled by an external process controller 120. Theprocess controller 120 includes the user interface 116, a computer 122,and a serial port concentrator 124. The compounder pump 102 and theblood pumps 104 are in communication with the process controller 120through the serial port concentrator 124, for example, over RS-232communication links. The blood processing system 100 typically includesa tubing sealer 130 for sealing plastic tubing as necessary for variousblood processing operations. The blood processing system 100 typicallyincludes an uninterruptible power supply (UPS) 128 for maintainingelectrical power to the 12-Volt power supply, the process controller,and other components in the event of a primary power loss.

FIG. 1C shows an exemplary wiring diagram for another embodiment of theblood processing system 100. The blood processing system 100 may includea printer in communication with the process controller for printing outreports. The blood processing system 100 may include a card reader 134in communication with the process controller for card-based operatoridentification. The blood processing system 100 may include a wirelessbar code scanner base station 138 in communication with the processcontroller for receiving bar code information scanned using a wirelessbar code scanner 136. Bar codes are typically used to track the varioussolution containers and the pumps on which those containers wereprocessed.

The process controller 120 coordinates the actions of the compounderpump 102, the blood pumps 104, and the operator throughout the variousmixing operations, as described in greater detail in Application D72.The process controller 120 initiates high level embedded commands withinthe pumps to move and mix the fluids. The process controller 120instructs the operator through the setup and teardown of each processthrough the user interface 116. The user interface 116 is also used toinform the operator of any anomalies that may occur during mixingoperations.

When the blood processing system 100 is operating from theuninterruptible power supply 128 and at other appropriate times, theprocess controller 120 will prevent compounding and other pumpoperations from starting, although the pumps will generally be allowedto complete any ongoing operations. Furthermore, if the processcontroller fails, the pumps have internal logic for safely completing orterminating any ongoing operations.

Blood Disposables

In an exemplary embodiment of the present invention, the processcontroller 120 coordinates blood processing for an entire bank of fiveblood pumps 104 at a time. Specifically, five pump cassettes, eachconnected to a RBCC container and an incubation bag for receiving theincubation solution, are loaded respectively into the five blood pumps104. The five pump cassettes are preferably connected by a singleworking solution inlet tube to the working solution container so thatall five blood pumps draw working solution from the single workingsolution container. For convenience, the five interconnected pumpcassettes along with their respective incubation bags and variousplastic tubing may be referred to hereinafter as a “blood disposablesset.” The blood disposables set is preferably used for a single bloodprocessing cycle and is then discarded. The blood disposables set isdescribed in greater detail in Application D85.

FIG. 2 shows an exemplary blood disposables set 200 in accordance withan embodiment of the present invention. The blood disposables set 200includes five pump cassettes 202 ₁₋₅, each respectively having a RBCCinlet tube 204 ₁₋₅ connected to an RBC inlet port of the pump cassetteand an incubation solution outlet tube 206 ₁₋₅ connected to an outletport of the pump cassette and to an incubation-bag 118 ₁₋₅. The blooddisposables set 200 also includes working solution distribution tubing212 that connects to a working solution inlet port on each pump cassette202 ₁₋₅ and to a single working solution inlet tube 210 so that theworking solution inlet ports of all pump cassettes 202 ₁₋₅ areeffectively connected to the single working solution inlet tube 210. Theworking solution inlet tube 210 preferably connects to the workingsolution distribution tubing 212 close to where the working solutioninlet port of the middle pump cassette 202 ₃ connects to the tubing 212,and the working solution inlet ports of each concentric pair of pumpcassettes is preferably connected to the tubing 212 a substantiallyequal distance from that center connection such that the workingsolution inlet ports of the pump cassettes 202 ₁ and 202 ₅ areessentially equidistant from the center connection and the workingsolution inlet ports of the pump cassettes 202 ₂ and 202 ₄ areessentially equidistant from the center connection. Among other things,this spacing of pump cassettes along the tubing 212 facilitates primingof the pumps, as discussed below. In order to perform blood processing,each RBCC inlet tube 204 is connected to a separate RBCC container 106,and the working solution inlet tube 210 is connected to the commonworking solution container 112. The blood disposables set 200 alsoincludes six break-away closures 214, one on each of the RBCC inlettubes 204 and one on the working solution inlet tube 210. In order toreduce the likelihood of confusing which RBCC bag and which incubationbag is associated with each pump cassette, the RBCC inlet tubes 204 andthe incubation solution outlet tubes 206 are preferably coded, forexample, by alternating between color-striped and clear tubing fromcassette to cassette.

FIG. 3A shows a front view of the pump cassette 202 in accordance withan embodiment of the present invention. The pump cassette 202 isessentially a rigid core including formations and sealing ribs 340constituting various pumping chambers, fluid valves, and fluid pathways(channels). The rigid core is covered on each side by a flexiblemembrane (e.g., a flexible PVC sheet). The flexible membranes sealagainst the core and isolate the blood pump 104 from fluids within thecassette. The pump cassette 202 is designed to interface with the bloodpump 104 in only one direction. For example, the pump cassette 202typically includes an asymmetric feature (such as the placement oftubing) that prevents the blood pump door from closing if the pumpcassette 202 is inserted incorrectly.

Among other things, the pump cassette 202 includes a working solutioninlet port 304, an RBC inlet port 305, a vent port 307, an outlet port308 and two pumping chambers, namely a working solution chamber 333 andan RBC chamber 334. During blood processing, working solution from theworking solution container 112 is drawn into the working solutionchamber 333 through the tubing 210 and 212 and the working solutioninlet port 304, and is pumped from the working solution chamber 333 intothe channel 310 while RBCC from the RBCC container 106 is drawn into theRBC chamber 334 through the RBCC inlet tube 204, the RBCC inlet port305, and the channel 310. This causes the working solution and RBCC tobe mixed within the channel 310 and the RBC chamber 334. The mixture(incubation solution) is pumped from the RBC chamber 334 to theincubation bag 118 through the outlet port 308 and the incubationsolution outlet tube 206.

FIG. 3B shows a rear view of the pump cassette 202 in accordance with anembodiment of the present invention. The rears view of the pump cassette202 shows various “volcano” valves that are used to open and closevarious fluid pathways within the pump cassette 202. The valves includean RBC priming valve 326, an RBC valve 328, an incubation bag valve 330,a working solution valve 332, and a working solution connection to RBCline valve 336. The volcano valves and the pumping chambers are alloperated pneumatically from the rear of the pump cassette 202, asdiscussed below.

Blood Pump

As discussed above, each blood pump 104 prepares incubation solution bymixing an anti-pathogen solution with RBCC. A disposable pump cassette202 is used to handle the various fluids. The pump cassette 202 servesas an interface between the blood pump 104, the RBCC container 106, andthe incubation bag 118 so that no working solution, RBCC, or incubationsolution comes into actual contact with the components of the blood pump104. The blood pump 104 preferably uses pneumatics to operate the pumpcassette 202 as well as other components, as discussed below.

The blood pump 104 produces the incubation solution by causing workingsolution to be drawn into the working solution chamber 333 and pumpingworking solution from the working solution chamber 333 into the channel310 while drawing RBCC into the RBC chamber 334 through the channel 310.This causes the working solution and RBCC to be mixed within the channel310 and the RBC chamber 334. The mixture (incubation solution) is pumpedfrom the RBC chamber 334 to the incubation bag 118 through the outletport 308.

In a typical embodiment of the present invention, the working solutionis pumped from the working solution chamber 333 using a pulsingtechnique in which small quantities of working solution are pumped atpredetermined intervals and the pulsing of working solution is adjustedperiodically using a closed feedback loop in order to produce anincubation solution having a predetermined concentration of workingsolution, with predetermined limits. Specifically, the working solutionis delivered in a pulsatile mode where the pulse width of the exit valveon the working solution chamber is controlled. The fluid valve is pulsedat a pulse width and interval that is predetermined for each pumpingstroke and is adjusted stroke-by-stroke according to the amounts ofworking solution and RBCC pumped, as described below. The blood pump 104can support pulse widths above some minimum value, and the intervalbetween pulses is increased in order to achieve an effective pulse widthbelow the minimum value.

The blood pump 104 preferably includes a library of generic pump control(N-Pump) functions. The N-Pump library functions are used to performvarious generic pumping operations such as, for example, pumping fluidinto a chamber of the pump cassette, pumping fluid out of a chamber ofthe pump cassette, measuring the mount of fluid pumped, performing airdetection, and maintaining tank pressures. The blood pump 104 preferablyalso includes a Fluid Logic Module (FLM) that contains higher levelfunctions that employ the N-Pump library functions to implementapplication-specific functions (such as specific logic for mixing theworking solution with the RBCC to produce the incubation solution).

The blood pump 104 includes one master board connected to two pumpboards that together perform the N-Pump and FLM functions. The masterboard communicates to each of the pump boards via a multi-drop RS-485bus. Each pump board controls a single pump chamber of the pump cassette202 and the valves on its board.

FIG. 4 shows a conceptual block diagram of the blood pump 104 inaccordance with an embodiment of the present invention. Among otherthings, the blood pump 104 includes a door assembly 402, an occluderassembly 404, a front plate assembly 408, a pneumatic control assembly410, a power/communication interface 412 including connectors for the12-Volt power supply and the RS-232 communication link to the processcontroller 120, and chassis components 414. Each of these assemblies isdiscussed below.

Pneumatic Control Assembly

The pneumatic control assembly 410 provides positive and negative airpressure for operating the various other pneumatically controlledcomponents and also acts as the general controller for the blood pump104. The pneumatic control assembly 410 contains three electromechanicalpump module assemblies, namely a tank management module assembly and twochamber module assemblies (one for the working solution pump chamber andone for the RBC pump chamber). Each pump module assembly includes analuminum manifold, pneumatic valves, pneumatic fittings, a valveinterface board, and an electronics board that includes pressuretransducers and a dedicated microprocessor. The tank management moduleassembly handles all communication between the blood pump and theprocess controller 120, synchronizes pumping of the chamber moduleassemblies, maintains positive and negative air pressure in variousaccumulators, seals and unseals the door assembly, engages anddisengages the occluders, monitors the door open/closed status, andmonitors the air-in-line sensor, as described below. Each chambermanagement assembly controls a separate one of the pump chambers, andalso controls the fluid valves associated with the pump chamber andmeasures the volume of liquids pumped through the pump chamber.

FIG. 5A is an architectural flow diagram showing the relationshipbetween the pneumatic control assembly 410 and the other assemblies inaccordance with an embodiment of the present invention. In this figure,the pneumatic control assembly 410 is represented by master module 512,accumulator assembly 513, working solution pump module 514, and RBCCpump module 515. The air pump 511 is considered to be one of the chassiscomponents 414. The air pump 511 generates high and low air pressure forthe master module 512, which stores high and low air pressure in theaccumulator assembly 513. The pneumatic control assembly 410 directs airpressure (positive and negative) to the various pneumatic mechanisms ofthe pump. The master module 512 pneumatically controls bladders in theoccluder assembly 404 and a bladder in the door assembly 402, asdiscussed below. The master module 512 provides high and low airpressure to the working solution pump module 514 and the RBCC pumpmodule 515. The working solution pump module 514 controls the workingsolution chamber 333 and associated valves of the pump cassette 202through the front plate assembly 408, and the RBCC pump module 515controls the RBC chamber 334 and associated valves of the pump cassette202 through the front plate assembly 408, as described below.

FIG. 5B shows an exemplary embodiment of the pneumatic control assembly410 in accordance with an embodiment of the present invention. Amongother things, the pneumatic control assembly 410 includes manifoldmounting bracket 502, a negative pressure accumulator (pressure bottle)513 a, a positive pressure accumulator (pressure bottle) 513 b, a manualdoor vent mechanism 503, the Tank Management Module Assembly 512, thetwo Chamber Module Assemblies 514 and 515, and associated tubing andfittings.

The tank management module 512 includes an input/output (I/O) board, aCPU board, a valve-interface board, a pneumatic manifold system,pneumatic valves, pressure transducers 2-vent covers (mufflers),stand-offs, and associated tubing and fittings. The tank managementmodule 512 is used to control the pressures in the accumulators 513, abladder in the door assembly 402, and bladders in the occluder assembly404. The I/O board contains electrical controls for controlling LEDsthat provide status information to the operator. The pressuretransducers are used to monitor the pressures of the accumulators 513and the bladder in the door assembly 402.

In the un-powered state, the pneumatic valve that controls flow to thebladder in the door assembly 402 preferably shuts closed. This preventsthe door from being opened in the event of a loss of power.

In the un-powered state, the pneumatic valves that control flow to thebladders in the occluder assembly 404 are preferably channeled to vent.This causes the occluders to occlude the tubing to prevent further flowof fluid through the tubing, as discussed below.

Each chamber module 514 and 515 includes a CPU board, a valve interfaceboard, pneumatic manifold system, pneumatic valves (including a VSO(variable) valve), a VSX chamber (504 and 505 respectively), O-ring,copper mesh, vent cover (muffler), stand-offs, pressure transducers, andassociated tubing and fittings. Each chamber module assembly controlsthe pneumatics for one of the pumping chambers and its associatedvalves. The VSX chambers 504 and 505 act as reference volumes in orderto measure the volume of fluid that is delivered with the FMS system.The pressure transducers are used to monitor the pressure of the VSXchamber, and of the pumping chamber. The positive pneumatic systemcontains a pressure relief valve to prevent the air pump frompressurizing the positive system to greater than 16.0 psig.

In the un-powered state, all of the pneumatic valves preferably open thefluid valves to the positive pressure line. This ensures that the fluidvalves are closed if there is a loss of power.

The blood pump 104 typically includes three microprocessor systems, oneon the tank management module 512 and one on each of the chamber modules514 and 515. These three microprocessor systems monitor each other fornormal operation. Each microprocessor system also monitors key internalprocesses and data for validity. If any of these monitors fail, afailsafe line permits any of the three processors to stop pumpingoperations, close all of the fluid valves and occluder, and send ananomaly signal to the process controller. If the blood pump 104 detectsan anomaly with the commands received from the process controller (e.g.,commands received out of sequence), then the blood pump 104 will stopfluid flow and send an anomaly signal to the process controller.

FIG. 5C shows an exemplary embodiment of the air pump 511 in accordancewith an embodiment of the present invention. The air pump 511 includes apump motor 591 mounted to a pump plate 592 using double-sided tape 594and two miniature nylon cable ties 595. Four ribbed isolator grommets593 are inserted into corresponding openings in the pump plate 592.

Front Plate Assembly

The front plate assembly 408 includes all necessary pneumatic pathwaysto interface to the disposable pump cassette 202. The front plateassembly 408 includes a bezel and a bezel gasket through which the pumpcassette 202 is operated. During operation of the blood pump 104, thepump cassette 202 is positioned in the door assembly 402 and is pressedagainst the front plate assembly 408 in alignment with the bezel andbezel gasket by a bladder in the door assembly 402, as discussed below.Air lines connected to the bezel from the pneumatic control assembly 410are used to displace membranes of the bezel gasket to operate thevarious valves and chambers of the pump cassette 202.

FIG. 6A shows an exploded view of an exemplary front plate assembly 408in accordance with an embodiment of the present invention. Among otherthings, the front plate assembly 408 includes a rigid front plate 602 towhich are mounted a bezel 604, chamber foam 606, spacer 608, air-in-linesensor 610, bezel gasket 612, gasket retainer 614, hardware 616, dowelpins 618, and grommet 620. The bezel 604, chamber foam 606, and bezelgasket 612 are mounted to the front plate 602 by the gasket retainer 614and associated hardware 616, forming a bezel assembly. This bezelassembly is used to control pumping and mixing of fluids using the pumpcassette 202, as described below. The front plate 602 includes holes forallowing air tubes to pass between the rear of the bezel 604 and thepneumatic control assembly 410, which is typically situated behind thefront plate 602. The front plate 602 also includes openings for occluderblades and for engaging a door latch mechanism, as described below. Theair-in-line sensor 610 is positioned so as to align with and engage theRBCC inlet tube 204, and is used during blood processing to detect airin the RBCC inlet tube 204 indicating that there is no more RBCC to beprocessed.

FIG. 6B shows a front view of an exemplary bezel 604 in accordance withan embodiment of the present invention. The bezel 604 is preferably amolded polycarbonate/ABS unit including, among other things, a workingsolution chamber cavity 633 for operating the working solution chamber333 of the pump cassette 202, an RBC chamber cavity 634 for operatingthe RBC chamber 334 of the pump cassette 202, and various valve cavities635 for operating the various valves of the pump cassette 202. Each ofthe chamber cavities 633 and 634 typically includes two air holes 638through which air is pumped into and out of the chamber cavity. Theworking solution chamber cavity 633 is preferably molded with ribstructures 636 that allow for airflow within the working solutionchamber cavity 633 but mechanically restrict the amount of workingsolution that can be drawn into the working solution chamber 333 of thepump cassette 202. The bezel with rib structures is described in greaterdetail in Application D75. The compounder 102 preferably uses the samemolded bezel 604 as the blood pump 104, but with the rib structures 636removed (e.g., by precision machining) to allow for greater pumpingcapacity.

FIG. 6C shows a rear view of the bezel 604 in accordance with anembodiment of the present invention. The bezel 604 includes integralsolvent bondable tubing connections (ports) 637 to which pneumatictubing from the pneumatic control assembly 410 are connected. In thisembodiment, each of the valve cavities 635 is associated with a singleintegral port 637, and each of the chamber cavities 633 and 634 areassociated with two integral ports 637. The integral ports 637 allow thepneumatic connections to be made without independent fittings andaccompanying O-rings.

FIG. 6D shows a front view of an exemplary bezel gasket 612 inaccordance with an embodiment of the present invention. The bezel gasket612 fits over the front of the bezel 604 and acts as an interfacebetween the bezel 604 and the pump cassette 202 for sealing the fluidpaths of the pump cassette 202 and for actuating the chambers and valvesof the pump cassette 202. The pump cassette 202 is pressed firmlyagainst the front side of the bezel gasket 612 during blood processingin order to produce an air-tight seal between the bezel gasket 612 andthe pump cassette 202. The bezel gasket 612 includes membranes thatcorrespond to the chamber cavities and valve cavities. Positive andnegative air pressure produced through the bezel cavities operate on thebezel gasket membranes, which in turn operate on the chambers and valvesof the pump cassette 202.

FIG. 6E shows a rear view of an exemplary bezel gasket 612 in accordancewith an embodiment of the present invention. The rear side of the bezelgasket 612 contacts the front side of the bezel 604, and is pressedfirmly against the bezel 604 during blood processing in order to producean air-tight seal. The bezel gasket 612 includes membranes thatcorrespond to the chamber cavities and valve cavities. Positive andnegative air pressure produced through the bezel cavities operate on thebezel gasket membranes, which in turn operate on the chambers and valvesof the pump cassette 202.

Door Assembly

The door assembly 402 mounts to the front plate assembly 408, andprovides a means to load and align the disposable pump cassette 202within the blood pump 104. The door assembly 402 provides a force on thepump cassette 202 against the bezel assembly of the front plate assembly408 in order to provide sealing of the cassette's fluid paths andvalves, as described in greater detail in Application D73. The doorassembly 402 includes a special latch system that helps maintain theseal, and also helps prevent accidental opening of the door during bloodprocessing, as described in greater detail in Application D74. The doorassembly 402 also provides a surface for the occluders to functionagainst, as described below.

FIG. 7A shows an exploded view of the door assembly 402 in accordancewith an embodiment of the present invention. Among other things, thedoor assembly 402 includes a door cowl 701, a latch spring post 702, adoor latch 703, a cassette receptacle 704, a back plate 705, a latch pin706, a bladder 707 with an attached pneumatic circuit 730, a frame 708,a door pin 709, a door mounting bracket 710, a piston assembly 711including a piston plate 731 and a piston cover 732, a human interfaceboard assembly 712, double coated tape 713, a miniature cable tie 714,recessed bumpers 715, E-rings 722, cable tie mount 723, torsion springs724 and 725, extension spring 726, a cassette orientation tab 799, andvarious screws 716, 717, 718, 719, 720, and 721. The human interfaceboard assembly 712 is mounted to the inside of the door cowl 701. Thepiston assembly 711 includes a rigid plate 731 having a protrusion thatis covered by the piston cover 732. The bladder 707, double coated tape713, and piston assembly 711 are sandwiched between the back plate 705and the frame 708, which are mechanically coupled together to form aframe assembly 750. The door latch 703 is positioned so that a handleportion is accessible from a front side of the door cowl 701. The frameassembly 750 is mounted to the inside of the door cowl 701 so that alatch portion of the door latch 703 protrudes through the frame assembly750 and the frame assembly 750 holds the door latch 703 in place. Thecassette receptacle 704 is pivotally mounted to the frame 708 using thedoor mounting bracket 710, the door pin 709, and the E-rings 722.Recessed bumpers 715 reduce strain on the door if the door is opened toofar or with excessive force. The torsion springs 724 and 725 aid theoperator in closing the door, as the door has considerable weight due tothe many components. The cassette orientation tab 799 prevents the doorfrom being closed if the pump cassette is oriented incorrectly in thecassette receptacle 704.

The bladder 707 is coupled to, and controlled by, a pneumatic circuit730 that provides positive and/or negative air pressure to the bladder707. Positive pressure supplied to the bladder 707 causes the bladder707 to expand in the direction of the frame 708. This, in turn, causesthe entire piston assembly 711 to move toward the control assembly 408,such that the piston cover 732 presses against the pump cassette 202and/or cassette receptacle 704, thereby producing an outward force onthe door 402 away from the control assembly 408. Alternatively,supplying negative pressure to the bladder 707 causes the pistonassembly 711 to move away from the pump cassette 202 and/or cassettereceptacle 704, thereby reducing the outward force on the door 402 awayfrom the control assembly 408.

The door assembly is designed to permit single-handed operation,specifically by pulling up on the handle. However, the door latch 703 isdesigned so that the door cannot be easily opened when the pump cassetteis in place in the cassette receptacle 704 with the door closed and thebladder 707 is inflated. Specifically, the latch portions of the doorlatch 703 have undercuts that are engaged by recesses in the front plateassembly 408. When the pump cassette is in place in the cassettereceptacle 704 with the door closed and the bladder 707 is inflated soas to push the pump cassette against the bezel components of the frontplate assembly 408, a sufficient force is generated between the doorassembly 402 and the front plate assembly 408 to prevent the door handlefrom being easily lifted. This door locking mechanism is described ingreater detail in Application D74.

FIG. 7B shows a front perspective view of the door assembly 402 inaccordance with an embodiment of the present invention. The humaninterface board assembly 712 having LEDs and the handle portion of thedoor latch 703 are visible from the front of the door cowl 701. Aportion of the cassette receptacle 704 and a portion of the pneumaticcircuit 730 are also visible.

FIG. 7C shows a rear perspective view of the door assembly 402 inaccordance with an embodiment of the present invention, in which thecassette receptacle 704 is in a retracted position. Visible at the rearof the door cowl 701 are the frame 708, the latch portion of the doorlatch 703, the cassette receptacle 704, the piston assembly 711, thedoor mounting bracket 710, the torsion springs 724 and 725, a portion ofthe human interface board assembly 712, and a portion of the pneumaticcircuit 730.

FIG. 7D shows a rear perspective view of the door assembly 402 inaccordance with an embodiment of the present invention, in which thecassette receptacle 704 is in an open position. Visible at the rear ofthe door cowl 701 are the frame 708, the latch portion of the door latch703, the cassette receptacle 704, the piston assembly 711, the doormounting bracket 710, the torsion springs 724 and 725, a portion of thehuman interface board assembly 712, and a portion of the pneumaticcircuit 730.

Occluder Assembly

The occluder assembly 404 mounts to the back of the front plate assembly408, and is used to selectively occlude the RBCC inlet tube 204, theincubation solution outlet tube 206, and the working solutiondistribution tube 212 as needed for testing, blood processing, andprotection in the event of a failure. In the blood pump 104, theoccluder assembly 404 includes two occluders, one operating on both theRBCC inlet tube 204 and the incubation solution outlet tube 206, and theother operating on the working solution distribution tube 212. Theoccluders are controlled pneumatically, and can be controlledindependently.

In a typical embodiment of the present invention, each occluder includesan occluder blade that is operated by a flat spring and an inflatablebladder. The occluder blade is coupled to one end of the spring. Whenthe bladder is deflated, the spring extends the occluder blade into anoccluding position, which blocks the passage of fluid through thetube(s). When the bladder is inflated, the bladder bends the spring soas to retract the occluder blade from the occluding position, whichenables the passage of fluid through the tube(s). In the event of a lossof pneumatics, the occluder defaults to the occluded position so as toprevent fluid from passing through the tubing.

FIG. 8 shows a side perspective view of the occluder assembly 404 inaccordance with an embodiment of the present invention. The occluderassembly 404 includes, among other things, a bottom housing 801, a tophousing 802, a first occluder having an occluder blade 813 and othercomponents operated pneumatically through tube 803, and a secondoccluder having an occluder blade 814 and other components operatedpneumatically through tube 804. The occluder assembly 404 is mounted tothe front plate assembly 408, with the occluder blades 813 and 814protruding through slots in the front plate assembly 804. The tubes 803and 804 are connected to the pneumatic control assembly 410.

FIG. 9 shows a cross-sectional view of an occluder in accordance with anembodiment of the present invention. Among other things, the occluderincludes a flat occluder spring 812 having a rear end coupled to the tophousing 802 and a front end coupled to the occluder blade 814, a bladder808 situated between the top housing 802 and the spring 812, the tube804 coupled to the bladder 808, and an adjuster 810 for adjusting theprotrusion of the occluder blade 814. When the bladder 808 is inflated,the occluder spring 812 is deflected downward at the middle so as toshorten the effective length of the occluder spring 812 and retract theoccluder blade 814. When the bladder 808 is deflated, the occluderspring 812 extends flat and therefore extends the occluder blade 814.The occluder blade 814 moves within guides (not shown) that allow thespring to extend and retract the occluder blade 814.

FIG. 10 shows an exploded view of the occluder assembly 404 inaccordance with an embodiment of the present invention. Among otherthings, the occluder assembly 404 includes enclosure top 802, enclosurebottom 810, a first occluder including an occluder blade 813, a shaft821, a front bracket 819, a rear bracket 817, a bladder 809, and a tube803, and a second occluder including an occluder blade 814, a shaft 820,a front bracket 818, a rear bracket 816, a bladder 808, and a tube 804.The occluder blade 813 mounts to the front bracket 819 via the shaft821, while the occluder blade 814 mounts to the front bracket 818 viathe shaft 820. The rear brackets 816 and 817 are mounted to theenclosure top 802 via shaft 825, blocks 826 and 827, and clamps 828 and829. The rear brackets 816 and 817 are held in a substantially fixedposition, although the rear brackets 816 and 817 are able to rotateabout the shaft 825 as needed for operation of the occluders. The frontbracket 819 is mounted to the enclosure top 802 via shaft 821 andsliding blocks 823 and 824, while the front bracket 818 is mounted tothe enclosure top 802 via shaft 820 and sliding blocks 822 and 823. Thefront brackets 818 and 819 are able to slide forward and backward alongchannels formed in the sliding blocks 822, 823, and 824 as needed foroperation of the occluders. Thus, the blocks 826 and 827 constrain theposition of the occluder blades and act as bearing surfaces as the rearshaft rotates, and the sliding blocks 822, 823, and 824 act as bearingsurfaces for the front shafts as the occluder blades are actuated andreleased. It should be noted that the present invention is not limitedto the block-type bearings shown, but rather various types of bushings,bearings, fixed blocks, moving blocks, or any combination thereof couldbe used to permit rotation of the rear shafts and/or brackets andtranslational movement of the front shafts. The occluder blades 813 and814 can be manually retracted if necessary. The edge of the occluderblades 813 and 814 that engages the tubing are typically rounded so asnot to cut or crease the tubing.

Chassis Components

The chassis components 414 include various mechanical hardwarecomponents that are not considered part of the other assemblies. Amongother things, the chassis components 414 include the DC air pump 511, achassis base, a door sensor (and cable), mounting foot grommets, skins(housing), and associated hardware and fasteners. The housing includes amounting point, on the back of the unit, for the manual piston bladder(door) vent 503.

Pump Cassette Handling

FIG. 11 is a schematic diagram showing the pump cassette 202 installedin the blood pump 104 in accordance with an embodiment of the presentinvention. The pump cassette 202 is installed in the cassette receptacle704. The door assembly 402 will only close if the pump cassette 202 isoriented correctly in the cassette receptacle 704, and will not close ifthe pump cassette 202 is inserted backwards so that the tubing connectedto the pump cassette 202 does not align with corresponding channels inthe door latch 703. When the door assembly 402 is closed and the bladderin the door assembly 402 is inflated, the pump cassette 202 is pressedtightly against the bezel gasket 612 and gasket retainer 614 on thefront panel assembly 408, the RBCC inlet tube 204 is captured by theair-in-line sensor 610 on the front plate assembly 408, the occluderblade 813 aligns with and occludes the working solution distributiontube 212, and the occluder blade 814 aligns with and occludes both theRBCC inlet tube 204 and the incubation solution outlet tube 206.

Blood Processing

As discussed above, the compounder 102 and the blood pumps 104 operateunder control of the process controller 120. In exemplary embodiments ofthe present invention, introduction of the anti-pathogen compound intothe RBCC is performed in two stages, a first stage in which theanti-pathogen compound is mixed with buffer solution to a firstconcentration to form the working solution, and a second stage in whichthe working solution is mixed with the RBCC to a second concentration toform the incubation solution. The two-stage process is described in moredetail in Application D72.

FIG. 12 shows a process flow diagram describing the compounding andblood treatment process, which is coordinated by the process controller120, in accordance with an embodiment of the present invention.Rectangular blocks indicate commands sent to the pump by the processcontroller 120. Rounded blocks indicate instructions sent to theoperator by the process control 120.

The process starts in block 1201. In block 1202, the process controllerinstructs the operator to load and scan a compounder disposable set.After the compounder disposable set is loaded into the compounder, theprocess controller instructs the compounder to run a dry cassetteintegrity test (CIT) in block 1203. Assuming the dry CIT is acceptable,the process controller instructs the operator to hang, scan, and connectthe buffer solution bag so that the buffer solution bag is connected tothe inlet port of the pump cassette, in block 1204. The processcontroller then instructs the compounder to prime the compounderdisposable set, in block 1205. The process controller then instructs thecompounder to run a wet CIT, in block 1206. Assuming the wet CIT isacceptable, the process controller then instructs the operator to scanand load the vial assembly and spike receptacle into the vial spikeassembly, in block 1207. The process controller then instructs thecompounder to spike the vial, in block 1208. Once spiking is completed,the process controller instructs the compounder to perform thecompounding operation, in block 1209. Compounding is described in moredetail in Application D70.

After compounding is complete, the process controller coordinates“teardown” of the compounder for removal and disposal of the compounderdisposable set from the compounder. Specifically, with reference againto FIG. 12, the process controller instructs the operator to heat sealthe working solution line, in block 1235, and then agitate and invertthe working solution bag, in block 1214. The process controller theninstructs the operator to heat seal the buffer solution line, in block1227. The process controller then instructs the operator to clamp thelines leading to the vial, in block 1228. The process controller theninstructs the compounder to release the compounder door, in block 1231,which is accomplished by deflating the bladder in the door assembly. Theprocess controller then instructs the compounder to release the bladderpressure on the vial spike (piston), in block 1232. The processcontroller then instructs the operator to remove the compounderdisposables from the compounder 1233.

After compounder “teardown” is complete, the process controllercoordinates the blood processing operations in which the RBCC is mixedwith working solution by the blood pumps 104 in order to produce theincubation solutions. Specifically, in block 1210, the processcontroller 120 instructs the operator to load and scan a blooddisposables set in one of the banks of blood pumps 104. The processcontroller 120 may instruct the operator to scan, for each blood pump,the RBCC bag 106, the blood pump 104, and the incubation bag 118. Theprocess controller 120 stores this information so that there is acorrelation between each blood pump 104 and the solutions processed andproduced by it. This information can be used, for example, to identifyall incubation solutions produced by a particular blood pump 104 if theblood pump 104 is found to be defective.

After the blood disposables set is loaded, the process controller 120instructs the blood pumps 120 to perform a dry CIT, in block 1212. Thedry CIT operation is described in more detail with reference to FIG. 14below. Assuming the dry CIT is successful, the process controller 120then instructs the operator to connect the working solution inlet tube210 of the blood disposables set to the working solution bag 112 usingthe sterile dock 114, in block 1213, and open the break-away closure onthe working solution inlet tube 210, in block 1215. The processcontroller 120 then coordinates working solution priming of the bloodpumps 104, in block 1216, and then performs a wet CIT on each of theblood pumps 104, in block 1217. The priming and wet CIT operations aredescribed in more detail respectively with reference to FIGS. 15 and 16below. Assuming the wet CIT is successful, the process controller 120instructs the operator to open the break-away closures on the RBCC inlettubes 204, in block 1218. These break-away closures are not openedearlier in order to prevent contamination of the blood in case of ablood pump failure.

After the break-away closures are opened, the process controller 120instructs the blood pumps 104 to mix the RBCC with the working solutionto produce the incubation solutions, in block 1219. The blood mixingoperation is described in more detail with reference to FIG. 17 below.

After blood mixing is complete, the process controller 120 instructs theoperator to heat seal the incubation solution outlet tubes 206, in block1220, and to heat seal the working solution distribution tubes 212, inblock 1221. The process controller 120 then instructs the blood pumps104 to test the heat seal on the incubation solution outlet tubes 206,in block 1223. Assuming the tubes are sealed, the process controller 120instructs the blood pumps 104 to release their respective doors, inblock 1224. The process controller 120 then instructs the operator toremove the incubation bags 118, in block 1225, and to tear down theblood disposables set, in block 1226.

If there is enough working solution remaining for another bloodprocessing cycle, then the process may recycle to block 1210 tocoordinate blood processing operations for another bank of blood pumps.If and when the working solution has expired or there is not enoughworking solution remaining for another blood processing cycle, then theprocess controller typically instructs the operator to remove theworking solution bag, in block 1236. The process ends in block 1234.

FIGS. 13A-B show a process flow diagram showing additional details ofthe blood processing operations in accordance with an embodiment of thepresent invention. The process begins in block 1301. A check is firstmade to confirm that the bank of blood pumps 104 is configured properly,in block 1302. This involves, among other things, confirming that thereis communication between the process controller 120 and the five bloodpumps 104, confirming that all five blood pumps 104 are configured tooperate as blood pumps, and confirming that all five blood pumps 104contain the correct version of embedded software. The process entersanomaly handling, in block 1303, if the bank is not configured properly.

If the bank is configured properly, then a determination is made as towhether there is a sufficient quantity of working solution and asufficient amount of time for performing the blood processing operation,in block 1304. If there is no working solution, then the compoundersetup and process operation is performed as described in ApplicationD70, in block 1308. If there is an insufficient amount of workingsolution, then the compounder teardown operation is performed asdescribed in Application D70, in block 1305, and, in block 1306, theoperator is given the option to either terminate the blood processingoperation, in which case the process ends in block 1333, or continue theblood processing operation, in which case the compounder setup andprocess operation is performed as described in Application D70, in block1308.

If there is a sufficient quantity of working solution in block 1304, orafter working solution is prepared in block 1308, the blood disposablesset is loaded into the blood pumps 104. If the occluders are engaged, inblock 1309, then the door is unsealed, in block 1310. Once the door isunsealed, the operator is instructed to load the blood disposables set,in block 1311, and to close the door. When the door is confirmed to beclosed, in block 1314, the operator is instructed to scan the RBCC bags,blood pumps, and incubation solution bags, in block 1313. When scanningis complete, in block 1314, the blood pumps 104 are instructed to sealtheir respective doors, in block 1315. If a door is unable to be sealed,then the process enters anomaly handling, in block 1316, which typicallyincludes instructing the operator to reload the pump cassette. If thedoor is able to be sealed, then the blood pumps 104 are instructed toperform the dry CIT, in block 1317. If the dry CIT fails, then theprocess enters anomaly handling, in block 1318, which typically involvesinstructing the operator to reload the pump cassette and running the dryCIT again. If the dry CIT passes, then the operator is instructed toconnect the working solution inlet tube 210 to the working solution bag112 using the sterile dock and to open the break-away closure on theworking solution line, in block 1319. The blood pumps 104 are theninstructed to perform the priming process, in block 1320. If the primingprocess fails, then the process enters anomaly handling, in block 1320.If priming is successful, then the blood pumps 104 are instructed toperform the wet CIT, in block 1322. If the wet CIT fails, then theprocess enters anomaly handling, in block 1323. If the wet CIT passes,then the operator is instructed to open the break-away closures on theRBCC inlet tubes, in block 1324. The blood pumps 104 are then instructedto mix the RBCC and the working solution to form incubation solution, inblock 1325. If there is a failure during mixing, then the process entersanomaly handling, in block 1326.

Assuming blood processing is successful, the operator is instructed toheat seal the incubation and working solution lines, in block 1327. Theblood units 104 are then instructed to test the seal on the incubationline, in block 1328. If the test fails, then the process enters anomalyhandling, in block 1329.

Assuming the incubation line is sealed, then the blood pumps 104 areinstructed to release their respective doors, in block 1330, after whichthe operator is instructed to teardown the blood disposables set, inblock 1331. A closed-case file is prepared, in block 1332. The processends in block 1333.

Blood Pump Dry Cassette Integrity Test

The dry cassette integrity test (CIT) is used to identify air leaks inthe cassette membranes prior to pumping any fluids. Identifying acassette with a membrane hole will protect the RBCC from beingcontaminated by a potentially non-sterile cassette, and will reduce thepotential of pumping fluid into the blood unit itself. Also, at the timeof the dry CIT, an internal pressure transducer calibration check isperformed in order to ensure that none of the transducers have failed ordrifted out of calibration. Also during the dry CIT, the fluid valveleading to the air vent on the cassette is tested by closing the valve,pressurizing the pump chamber, and observing the pressure decay.

FIG. 14 shows a process flow diagram describing the blood pump dry CITprocess in accordance with an embodiment of the present invention. Thedry CIT process begins in block 1401. The positive pneumatic system isfirst isolated from the cassette and a baseline leak rate for thepositive assembly is obtained, specifically by closing the workingsolution line occluder 813, in block 1402, opening all fluid valves andclosing the variable valves, in block 1403, measuring the positive tankleak rate, in block 1404, and generating an error signal if the positivetank leak rate is greater than or equal to the predetermined threshold,in block 1405.

Then, the negative pneumatic system is isolated from the cassette and abaseline leak rate for the negative assembly is obtained, specificallyby closing all fluid valves, in block 1407, measuring the positive tankleak rate, in block 1408, and generating an error signal if the negativetank leak rate is greater than or equal to a predetermined threshold, inblock 1409.

Then, the process tests the cassette sheeting of the valves outside ofthe volcano valves, specifically by opening the working solution lineoccluder 813, in block 1410, measuring the positive tank leak rate, inblock 1411, and generating an error signal if the positive tank leakrate is greater than or equal to a predetermined threshold, in block1412.

Then, the process tests the cassette sheeting at the center of thevolcano valves, specifically by opening valves 1A1 and 2A1 and all fluidvalves, in block 1413, measuring the positive and negative tank leakrates, in block 1414, and generating an error signal if the positive ornegative tank leak rate is greater than or equal to a predeterminedthreshold, in block 1415.

Then, the process verifies calibration of the positive transducers,specifically by isolating the positive transducers and connecting thepositive transducers together, in block 1416, measuring the positivetank leak rate, in block 1417, generating an error signal if thepositive tank leak rate is greater than or equal to a predeterminedthreshold, in block 1418, determining whether all positive transducersagree to within a predetermined threshold, in block 1419, and generatingan error signal if the positive transducers do not agree to within apredetermined threshold, in block 1420.

Then, the process verifies calibration of the negative transducers,specifically by isolating the negative transducers and connecting thenegative transducers together, in block 1421, measuring the negativetank leak rate, in block 1422, generating an error signal if thenegative tank leak rate is greater than or equal to a predeterminedthreshold, in block 1423, determining whether all negative transducersagree to within a predetermined threshold, in block 1424, and generatingan error signal if the negative transducers do not agree to within apredetermined threshold, in block 1425.

Finally, the process tests integrity of the fluid valve leading to thevent filter, specifically by filling the chamber, in block 1426,pressurizing the chamber, in block 1427, measuring the chamber leakrate, in block 1428, and generating an error signal if the chamber leakrate is greater than or equal a predetermined threshold, in block 1429.The dry CIT process ends in block 1430.

Blood Pump Priming

The working solution priming process operates on an entire bank of fiveblood pumps, where all blood pumps share a single working solution line.The working solution priming process is coordinated by the processcontroller 120 so as to prevent one pump from drawing in air that isbeing expelled by another pump, specifically by priming the operatingthe blood pumps symmetrically from the middle blood pump outward. Eachblood pump is responsible for detecting “no flow” conditions duringpriming and also for detecting air in the working solution chamber ofthe pump cassette 202 after the priming operation is complete. Thepriming process uses two operations, namely a “put” operation and a“get” operation. The “put” operation involves pumping the contents ofthe working solution chamber of the pump cassette 202 (air and/orworking solution) out through the working solution inlet 304 to theworking solution bag, specifically by applying a positive pressure tothe working solution chamber. The “get” operation involves drawing fromthe working solution inlet 304, specifically by applying a negativepressure to the working solution chamber. For convenience, the fiveblood pumps 104 in a bank are referred to numerically from one to five,where pump three is the middle pump of the bank, pumps two and four arethe pumps adjacent to the middle pump, and pumps one and five are theoutside pumps.

FIG. 15 shows a process flow diagram describing the blood pump workingsolution priming process in accordance with an embodiment of the presentinvention. The priming process begins in block 1501. In block 1502, aput operation is performed on all five blood pumps. This removes as muchair as possible from the working solution chambers of the pump cassettes102. Then, get operations are performed on the blood pumps, startingwith pump three, in block 1503, then pumps two and four simultaneously,in block 1504, and then pumps one and five simultaneously, in block1505. Then, put operations are performed on the blood pumps, startingwith pump three, in block 1506, then pumps two and four simultaneously,in block 1507, and then pumps one and five simultaneously, in block1508. Then, get operations are performed on the blood pumps, startingwith pump three, in block 1509, then pumps two and four simultaneously,in block 1510, and then pumps one and five simultaneously, in block1511. Then, put operations are performed on the blood pumps, startingwith pump three, in block 1512, then pumps two and four simultaneously,in block 1513, and then pumps one and five simultaneously, in block1514. Finally, get operations are performed on all five pumpssimultaneously, in block 1518. If a blood pump detects a “no flow”condition during any of the get and put operations, an error conditionis raised in block 1516, and priming is terminated. If a blood pumpdetects air in the working solution chamber after completion of thepriming process, then an error condition is raised in block 1517. Thepriming process ends in block 1518.

Blood Pump Wet Cassette Integrity Test

The wet cassette integrity test (CIT) is used to identify defects withinthe injection-molded body of the cassette. The wet CIT involves testingthe functionality of all of the fluid valves within the cassette as wellas testing for “cross-talk” between the fluid paths and fluid pumpchambers within the cassette. The wet CIT is performed on a partiallyprimed cassette, after priming the working solution pump chamber, butbefore priming the RBC pump chamber. Therefore, a complete wet CIT isperformed on the working solution pump chamber, but the RBC pump chamberis tested using air pressure and decay. Priming and wet testing of theRBC pump chamber is performed during blood mixing, as discussed below.

FIG. 16 shows a process flow diagram describing the blood pump wet CITprocess in accordance with an embodiment of the present invention. Thewet CIT process begins in block 1601, and involves three passes ofblocks 1602 through 1619. In each pass, the working solution lineoccluder 813 is retracted, in block 1602, and various measurements areperformed on both chambers, in block 1603. If the measurements areoutside of a predetermined threshold (NO in block 1604), then an errorsignal is generated, in block 1605. Otherwise, a chamber fillingoperation is performed, in block 1606. During the first pass, bothchambers are filled; during the second pass, only one chamber is filled;during the third pass, only the other chamber is filled. After thechamber filling operation, various measurements are performed on thechambers, in block 1607. If the measurements are outside of apredetermined threshold (NO in block 1608), then an error signal isgenerated, in block 1609. At this point, the working solution lineoccluder 813 is left retracted during the first pass, but is closedduring the second and third passes, in blocks 1610 and 1611. Therequired fluid valves are then opened, in block 1612, tank pressure isapplied to the chambers for a predetermined amount of time, in block1613, and various measurements are performed on the chambers, in block1614. If the measurements are outside of a predetermined threshold (NOin block 1615), then an error signal is generated in block 1616.Otherwise, the process determines whether the volume displaced is withinsome threshold, in block 1617. If not, then an error signal isgenerated, in block 1618. After all three passes are complete, theworking solution line occluder 813 is opened, in block 1620, and bothchambers are purged to the working solution bag, in block 1621. Theprocess ends in block 1622.

Blood Mixing

The blood mixing process is performed essentially in three stages,namely a priming stage, a mixing stage, and a residuals stage. Thepriming stage involves priming the RBC pump chamber 334 from the RBCCbag 106. The mixing stage involves repetitively drawing a quantity ofworking solution in to the working solution pump chamber 333 and drawinga quantity of RBCC through the channel 310 into the RBC pump chamber 334while pulsing working solution from the working solution pump chamber333 into the channel 310 so that the working solution and RBCC mixwithin the channel 310 and the RBC pump chamber 334. The pulsing ofworking solution is dynamically adjusted so that the resultingincubation solution has a predetermined concentration of workingsolution, within certain limits. The mixing stage continues until air isdetected in the RBCC inlet tube 204 by the air-in-line sensor 610,signaling that there is no more RBCC to be processed. The residualsstage handles the residual contents in the RBC pump chamber 334 (if any)following the mixing stage. In the residuals stage, the concentration ofworking solution and RBCC in the RBC pump chamber 334 is measured, andthe contents of the RBC pump chamber 334 are delivered to the incubationbag 118 if and only if the concentration of working solution and RBCC iswithin a predetermined specification. The overall concentration ofworking solution in the incubation solution is also measured, and asignal is generated to indicate whether or not the incubation solutionis usable. The blood mixing process preferably prevents fluid from beingpushed back into the working solution line after RBCC has beenintroduced into the pump cassette in order to prevent contamination ofthe working solution.

FIGS. 17A-D show a process flow diagram describing the blood mixingprocess in accordance with an embodiment of the present invention. Theprocess begins in block 1701, and proceeds to prime the RBC pump chamber334. Specifically, the RBC occluder 814 is opened, in block 1702, andthe contents of the RBC pump chamber 334 are purged to the RBCC bag 106,in block 1703. If a no flow condition is detected in block 1704, thenthe process ends in failure in block 1705. Otherwise, the RBC pumpchamber 334 is filled from the RBCC bag 106, in block 1706. If a no flowcondition is detected in block 1707, then the process ends in failure inblock 1705. Otherwise, the contents of the RBC pump chamber 334 ispurged back to the RBCC bag 106, in block 1708, and the volume of theRBC pump chamber 334 is computed, in block 1709. If a no flow conditionis detected in block 1710, then the process ends in failure in block1705. If air is detected in the RBC pump chamber 334 in block 1711, thenan error signal is generated, in block 1712, and a second attempt ismade to prime the RBC pump chamber 334 by repeating blocks 1706 through1711. If air is again detected in the RBC pump chamber 334 in block1711, then the process ends in failure in block 1713.

If the RBC pump chamber 334 is successfully primed, then the processcontinues with the mixing stage. Specifically, the working solution pumpchamber 333 is filled from the working solution bag 112 with workingsolution, in block 1714. The volume of the working solution pump chamber333 is measured, in block 1715. If air is detected in the workingsolution pump chamber 333 in block 1716, then the process ends infailure in block 1717. If a no flow condition is detected in block 1718,then the process ends in failure in block 1719.

The RBCC is then mixed with working solution, in block 1720,specifically by drawing RBCC from the RBCC bag 106 through the channel310 into the RBC pump chamber 334 while simultaneously pulsing workingsolution from the working solution pump chamber 333 into the channel 310so that the working solution and RBCC are mixed within the channel 310and the RBC pump chamber 334. While this mixing is being performed, theprocess is monitoring for air in the RBCC inlet tube 204, in block 1742.Assuming no air is detected in the RBCC inlet tube 204, in block 1742,the volumes of both chambers 333 and 334 are measured, in block 1721. Ifair is detected in the RBC pump chamber 334 in block 1722, then theprocess ends in failure in block 1723. If a no flow condition isdetected in block 1724, then the process ends in failure in block 1725.

After mixing the working solution and RBCC, the concentration of workingsolution to RBCC in the RBC pump chamber 334 is calculated, in block1726, and a determination is made whether the concentration for thisparticular chamber is within predetermined specifications, in block1727. If the concentration of working solution to RBCC in the RBC pumpchamber 334 is outside of specifications, then an error condition issignaled, in block 1728. In any case, though, the pulse width isadjusted based upon the concentration of working solution to RBCC in theRBC pump chamber 334, in block 1729, and the contents of the RBC pumpchamber 334 are delivered to the incubation bag 118, in block 1730. Thevolume of the RBC pump chamber 1731 is measured, in block 1731. If a noflow condition is detected in block 1732, then the process ends infailure in block 1733.

In this first pass of the mixing stage, from block 1734, the RBC pumpchamber 334 is filled from the RBCC bag 106, in block 1735. If a no flowcondition is detected in block 1736 while attempting to fill the RBCpump chamber 334 from the RBCC bag 106 then the process ends in failurein block 1737. Otherwise, the contents of the RBC pump chamber 334 arepurged to the RBCC bag 106, in block 1738, and the volume of the RBCpump chamber 334 is computed, in block 1739. If a no flow condition isdetected in block 1740 while attempting to purge the contents of the RBCpump chamber 334, then the process ends in failure in block 1741.Otherwise, the mixing stage continues by recycling to block 1714 andrepeating blocks 1714 through 1734. During the second and subsequentpasses of the mixing stage, the process recycles from block 1734 toblock 1714, omitting blocks 1735 through 1741.

When air is detected in the RBCC inlet tube 204, in block 1742, fillingof the RBC pump chamber 334 with RBCC and working solution is aborted(preferably before air has entered the RBC pump chamber), in block 1743,and a volume calculation is performed for both chambers, in block 1744.If air is detected in the RBC pump chamber 334 in block 1745, then theprocess ends in failure in block 1746. Assuming that there is no air inthe RBC pump chamber 334, then the concentration of working solution toRBCC in the RBC pump chamber 334 is calculated, in block 1747, and adetermination is made whether the concentration for this particularchamber is within predetermined specifications, in block 1748. If andonly if the concentration of working solution to RBCC in the RBC pumpchamber 334 is within specifications, the contents of the RBC pumpchamber 334 are delivered to the incubation bag 118, in block 1749, theRBC pump chamber 334 is filled from the RBCC bag 106, in block 1750,and, upon detecting air in the RBC pump chamber 334 in block 1751, thecontents of the RBC pump chamber 334 are delivered to the incubation bag118, in block 1752. Whether or not the residual contents of the RBC pumpchamber 334 are delivered to the incubation bag 118, the overallconcentration of working solution to RBCC in the incubation solution iscalculated, in block 1753. If the overall concentration is outside ofspecifications, then an error condition is signaled, in block 1755. Inany case, process data is sent to the process controller 120, in block1754. The process ends in block 1755.

Manual Teardown

During normal blood pump teardown, the blood pump 104 receives commandsfrom the process controller 120 to release pressure against the pumpdoor so that the door can be opened by the operator. The pressureagainst the door comes from both the door piston bladder and theoccluders. While the door piston bladder is pressurized and the tubingoccluders are engaged, it is virtually impossible for the operator toopen the pump door and remove the pump cassette. If communicationbetween the process controller 120 and the blood pump 104 is lost, thenthe operator will need to relieve this pressure manually in order toremove the cassette. Among other things, this involves the operatorpressing the manual door release valve on the back of the pump todeflate the bladder in the door assembly. The operator may also manuallyretract the occluders if necessary.

FIG. 19 shows a process flow diagram describing the process for manualblood pump teardown in accordance with an embodiment of the presentinvention. The process starts in block 1901. The operator is instructedto heat seal the incubation and working solution lines, in block 1902.The blood pump 104 is then instructed to test the heat seal of theincubation line, in block 1903. If the incubation line is not sealed,then the process enters anomaly handling, in block 1904. Assuming theincubation line is sealed, then the blood pump 104 is instructed to testthe heat seal of the working solution line, in block 1905. If theworking solution line is not sealed, then the process enters anomalyhandling, in block 1906. The blood pump 104 is instructed to release thedoor, in block 1907, and the operator is instructed to press the manualdoor release valve on the back of the pump to deflate the bladder in thedoor assembly, in block 1908, if the blood pump 104 does not release thedoor. The operator then manually retracts the occulders if necessary toallow opening of the door, in block 1909. The operator then removes theblood disposables, in block 1910. A close-case file is createdindicating the failure, in block 1911. The process ends in block 1912.

Volumetric Calibration

The blood pump 104 is typically calibrated periodically to verify itsability to accurately measure volumes of pumped fluids. In exemplaryembodiments of the invention, this calibration is done by running testmeasurements with two different test cassettes having different butknown chamber volumes.

FIG. 18 shows a process flow diagram describing the volumetriccalibration process in accordance with an embodiment of the presentinvention. The process begins in block 1801. The operator is instructedto scan a bar code on the blood pump 104 in block 1802 in order to testthe blood pump 104. The operator is then instructed to load the firsttest cassette, in block 1803. Upon confirmation that the door is closed,in block 1804, the door is sealed, in block 1805. If the door fails toseal properly, then the process enters anomaly handling, in block 1806.If the door seals properly, a dry CIT is run, in block 1807. If the dryCIT fails, then the process enters anomaly handling, in block 1808. Ifthe dry CIT passes, then a volume calibration test is run to measure thevolume of the chambers, in block 1809. If the difference between themeasured volume and the known volume of the first cassette is greaterthan or equal to some predetermined threshold, then the process entersanomaly handling, in block 1810. Otherwise, the door is released, inblock 1811, and the operator is instructed to load the second testcassette, in block 1812. Upon confirmation that the door is closed, inblock 1813, the door is sealed, in block 1814. If the door fails to sealproperly, then the process enters anomaly handling, in block 1815. Ifthe door seals properly, a dry CIT is run, in block 1816. If the dry CITfails, then the process enters anomaly handing; in block 1817. If thedry CIT passes, then a volume calibration test is run to measure thevolume of the chambers, in block 1818. If the difference between themeasured volume and the known volume of the second cassette is greaterthan or equal to some predetermined threshold, then the process entersanomaly handling, in block 1819. Otherwise, a test pass determination ismade, in block 1820, and a report is printed, in block 1821. The door isreleased, in block 1822, and the operator is instructed to remove thesecond test cassette, in block 1823. The process ends in block 1824.

It should also be noted that the flow diagrams are used herein todemonstrate various aspects of the invention, and should not beconstrued to limit the present invention to any particular flow orimplementation. In some cases, certain process steps can be omitted orperformed in a different order than shown without changing the overallresults or otherwise departing from the true scope of the invention.

The present invention may be embodied in other specific forms withoutdeparting from the true scope of the invention. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive.

1. A method for mixing a first liquid with a second liquid, the methodcomprising: actuating a first pump chamber of a membrane pumpingapparatus by applying fluid pressure to the membrane to pump a firstliquid into the first pump chamber through a channel of the membranepumping apparatus; and actuating a second pump chamber of the membranepumping apparatus by applying fluid pressure to the membrane to pump aquantity of a second liquid from the second pump chamber into one of thechannel and the first pump chamber so as to mix the first liquid and thesecond liquid within the first pump chamber.
 2. A method according toclaim 1, wherein the second pump chamber is actuated by applying fluidpressure to the membrane to pump the second liquid into one of thechannel and the first pump chamber during said pumping of the firstliquid.
 3. A method according to claim 1, wherein the membrane pumpingapparatus is a pump cassette having pneumatically operated first andsecond pump chambers and a plurality of pneumatically operated valves,and wherein actuating the first and second pump chambers comprising:pneumatically operating the pump chambers and the valves.
 4. A methodaccording to claim 1, wherein actuating the second pump chamber to pumpthe quantity of the second liquid comprising: actuating the second pumpchamber by applying fluid pressure to the membrane in a pulsatile mode.5. A method according to claim 4, wherein the pulsatile mode ischaracterized by a pulse width and pulse interval, and wherein themethod further comprising: determining a concentration of first liquidand second liquid in the first pump chamber; and dynamically adjustingat least one of the pulse width and pulse interval based on theconcentration of first liquid and second liquid in the first pumpchamber.
 6. A method according to claim 5, further comprising: actuatingthe second pump chamber by applying fluid pressure to the membrane topump a second quantity of the second liquid from the second pump chamberinto one of the channel and the first pump chamber using at least one ofthe dynamically adjusted pulse width and the dynamically adjusted pulseinterval.
 7. A method according to claim 1, further comprising:actuating the first pump chamber by applying fluid pressure to themembrane to pump the contents of the first pump chamber to a receptacle.8. A method according to claim 7, wherein the receptacle is external tothe membrane pumping apparatus.
 9. A method according to claim 1,wherein the first pump chamber receives the first liquid from a firstliquid container external to the membrane pumping apparatus.
 10. Amethod according to claim 1, further comprising: prior to actuating thesecond pump chamber by applying fluid pressure to the membrane to pumpthe quantity of the second liquid from the second pump chamber,actuating the second pump chamber by applying fluid pressure to themembrane to pump second liquid into the second pump chamber from asecond liquid container.
 11. A method according to claim 10, wherein thesecond liquid container is external to the membrane pumping apparatus.